John Pagel’s research offers hope with novel treatment combination for older patients

Nov. 9, 2009

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By Dean Forbes

“The results appear to be very encouraging and warrant us to study it further for patients who really have no significant other curative options,” said Dr. John Pagel, lead investigator.

Photo by Carol Insalaco

For the first time, Clinical Research Division investigators used a radiolabeled antibody to deliver targeted doses of radiation, followed by a stem cell transplant, to successfully treat a group of leukemia and pre-leukemia patients for whom there previously had been no other curative treatment options. Results of the study, led by Dr. John Pagel, appeared online Sept. 28 in the journal Blood.

All 58 patients, with a median age of 63 and with advanced acute myeloid leukemia or high-risk myelodysplastic syndrome—a pre-leukemic condition—went into remission after treatment with a novel combination of low-intensity chemotherapy, targeted radiation delivery by an antibody and a stem cell transplant. Forty percent of the patients were alive a year after treatment and approximately 35 percent had survived three years, about the same rates as patients who received similar treatment but whose disease was already in remission and who faced lower risk of relapse when therapy began.

The purpose of the study was to find the maximum dose of radiation that patients could tolerate with acceptable toxic side effects, not to assess how effective the new treatment was, according to Pagel and his colleagues at the Hutchinson Center, University of Washington and Pacific Northwest Laboratory. However, “the results appear to be very encouraging and warrant us to study it further for patients who really have no significant other curative options,” Pagel said.

Older (over age 50) patients with active, advanced leukemia and myelodysplastic syndrome pose the most difficult treatment challenges because standard transplant therapy rarely works, according to Pagel. Both standard and reduced intensity transplants usually require that patients be in remission.

Most of the study patients had active relapsed disease that in many cases had failed to respond to standard therapies. “These were people who had extremely advanced high-risk disease, they were typically older—most of them were in their 60s and some were in their 70s—and had few or no other options for a potential cure,” Pagel said.

The study used a radiolabeled antibody to deliver targeted amounts of radiation to leukemic cells, a technique developed several years ago at the Center. Delivered intravenously, this approach results in a two- to four-fold increase in the amount of radiation that reaches cancerous cells as compared to standard external beam radiation.

Pagel said further research is needed to test more patients at the highest radiation dose both at the Center and at other transplant centers around the country.

Grants from the National Institutes of Health, the Leukemia and Lymphoma Society of America, the Damon Runyon Cancer Research Foundation, the Edson Foundation and the Frederick Kullman Memorial Fund supported this research.